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DCLK1 autoinhibition and activation in tumorigenesis

2018年中国肿瘤标志物学术大会暨第十二届肿瘤标志物青年科学家论坛

作者： Wang Lai Hu Lei Jin An Xu Yu fang Wang rick f.thorne Xu Dong Zhang Mian Wu Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Disease CAS Centre for Excellence in Cell and Molecular Biology Innovation Centre for Cell Signalling Network School of Life Sciences University of Science and Technology

The list of long noncoding RNAs(lncRNAs) involved in the p53 pathway of the DNA damage response is rapidly expanding, but whether lncRNAs play a role in maintaining the de novo structure of DNA is unknown. Here we demonstrate that the p53-responsive lncRNA GUARDIN is important for maintaining genomic integrity under steady-state conditions and after exposure to exogenous genotoxic stress. GUARDIN is necessary for preventing chromosome end-to-end fusion through maintaining the expression of telomeric repeat-binding factor 2(TRf2) by sequestering microRNA-23 a. Moreover, GUARDIN also sustains breast cancer 1(BRCA1) stability by acting as an RNA scaffold to facilitate the heterodimerisation of BRCA1 and BRCA1-associated RING domain protein 1(BARD1). As such, GUARDIN silencing triggered apoptosis and senescence, enhanced cytotoxicity of additional genotoxic stress, and inhibited cancer xenograft growth. GUARDIN may therefore constitute a target for cancer treatment.

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The Innovation 2022年第1期3卷 46-53页

作者： Linna Cheng Zejing Yang Wenhao Guo Chengyong Wu Shufang Liang Aiping Tong Zhongwei Cao rick f.thorne Sheng-Yong Yang Yamei Yu Qiang Chen State Key Laboratory of Biotherapy and Cancer Center West China HospitalSichuan Universityand Collaborative Innovation Center of BiotherapyChengdu 610041China Institute of Hematology Henan Key Laboratory of Stem Cell Differentiation and ModificationHenan Provincial People’s HospitalPeople’s Hospital of Zhengzhou UniversityPeople’s Hospital of Henan UniversityZhengzhou 450003China Department of Abdominal Oncology Cancer Center and State Key Laboratory of BiotherapyWest China HospitalWest China Medical SchoolSichuan UniversityChengdu 610041China Translational Research Institute Henan Provincial People’s HospitalAcademy of Medical ScienceZhengzhou UniversityZhengzhou 450003China

Doublecortin-like kinase 1(DCLK1)is upregulated in many tumors and is a marker for tumor stem *** evidence suggests DCLK1 constitutes a promising drug target for cancer ***,the regulation of DCLK1 kinase activity is poorly understood,particularly the function of its autoinhibitory domain(AID),and,moreover,no physiological activators of DCLK1 have presently been *** we determined the first DCLK1 kinase structure in the autoinhibited state and identified the neuronal calcium sensor HPCAL1 as an activator of *** C-terminal AID functions to block the ATP-binding site and is competitive with ***1 binds directly to the AID in a Ca^(2+)-dependent manner,which releases the *** also analyzed cancer-associated mutations occurring in the AID and elucidate how these mutations disrupt DCLK1 autoinhibition to elicit kinase activity *** results present a molecular mechanism for autoinhibition and activation of DCLK1 kinase activity and provide insights into DCLK1-associated tumorigenesis.

关键词： inhibited tumorigenesis DCL

Optimizing calcination of coal by-products for maximizing REE leaching recovery and minimizing Al,Ca,and fe contamination

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Journal of Rare Earths 2024年第7期42卷 1354-1365,I0006页

作者： Tushar Gupta Ahmad Nawab rick Honaker MP Materials Mountain Pass Mine 67750 Bailey RoadMountain PassCA92366USA Department of Mining Engineering University of KentuckyLexingtonKY40506USA

High-temperature calcination is effective in improving the leaching characteristics of rare earth elements(REEs)from conventional REE-bearing minerals by transforming them into more leachable ***,the recovery of contaminants such as Al,fe,and Ca also increases *** objective of the study was to maximize the REE extraction while minimizing the concentration of contaminant ions(Al,Ca,and fe)in the leach *** density fractions of the coarse refuse from the Baker and fire Clay seam coal refuse were pulverized to a top size of 180μm and used as a feedstock for the *** the samples generated from thermal treatment were leached at 1%(w/v)using 1.2 mol/L sulfuric acid at 75℃ for 2 *** results from a parametric program based on a Box-Behnken design were used for modeling and optimization of three operating parameters associated with the lab-scale calcination *** parameters included temperature(400-800℃),ramp rate(2-10℃/min)and holding time(0-120 min).It was determined that the calcination temperature was the most significant parameter influencing REE *** majority of the heavy rare earth elements(HREEs)were found to be present in an insoluble form in the calcination products and were marginally affected by thermal treatment.A strong correlation between light rare earth elements recovery(LREEs)and Al suggested a possible association with *** optimum operating conditions for high REE recovery with comparatively lower contaminant concentration for 1.6 specific gravity float and 2.2 sink fractions of Baker and fire Clay seam material were determined to be at 776,800℃ and 407,800℃,calcining temperatures,respectively.A higher optimum temperature of 1.6 float fraction of Baker seam relative to fire Clay seam material was due to elevated pyrite concentration in Baker seam *** treatment at 400℃ converted pyrite into a soluble intermedium iron oxide,resulting in a high fe content in the ***

关键词： Calcination Optimization Rare earth elements Coal refuse

Invasive weed disrupts facilitation of nutrient uptake in grass-clover assemblage

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Soil Ecology Letters 2024年第1期6卷 89-96页

作者： Wei Zhang rick Muir Nicholas Dickinson faculty of Agriculture and Life Sciences Lincoln UniversityLincoln 7647New Zealand

Nutrient constraints in low-fertility soil were modified by different species ***-clover assemblages benefited both species in terms of nutrient *** of competition and facilitation is *** invasive weed removed essential nutrients from the grazing *** investigate the interplay of competition and facilitation between plants in low-fertility pasture grasslands of New Zealand,we compared nutrient uptake and acquisition of key nutrients of three species from different func-tional *** of Pilosella officinarum(mouse-eared hawk-weed,an invasive weed),Trifolium repens(white clover,a nitrogen fixer)and Dactylis glomerata(cocksfoot,a pasture grass)were planted into a soil with low-to-deficient concentrations of key *** yields were achieved by the grass growing alone but,when the clover and grass had grown together,there were complementary benefits in terms of procurement of a wide range of nutrients from soil despite lower root *** inva-sive weed negated these benefits,and soil nutrients were exploited less efficiently when Pilosella had grown alone or in a mixture with the other *** from the weed removed the benefits of grass-legume *** findings are interpreted to suggest that requirements for legumes to be the main source of nitrogen in pasture grasslands may be compromised unless competitive weeds are controlled to avoid disrupted procurement of key *** is likely these constraints to nutrient procurement would similarly impact conservation grasslands.

关键词： soil ferility facilitation species coexistence weed invasion legumes

Is Helicobacter pylori infection protective against esophageal cancer?

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World Journal of Gastroenterology 2024年第38期30卷 4168-4174页

作者： rick Maity Arkadeep Dhali Jyotirmoy Biswas General Medicine Institute of Post Graduate Medical Education and ResearchKolkata 700020India Department of Gastroenterology Sheffield Teaching Hospitals NHS Foundation TrustRoyal Hallamshire HospitalSheffield S102JFUnited Kingdom School of Medicine and Population Health University of SheffieldSheffield S102HQUnited Kingdom Deanery of Clinical Sciences University of EdinburghEdinburgh EH164SBUnited Kingdom Department of General Medicine College of Medicine and Sagore Dutta HospitalKolkata 700058India

Helicobacter pylori(***)infection affects a substantial proportion of the global population and causes various gastric disorders,including gastric *** studies have found an inverse relationship between *** infection and eso-phageal cancer(EC),suggesting a protective role against *** editorial focuses on the possible mechanisms underlying the role of *** infection in EC and explores the role of gut microbiota in esophageal carcinogenesis and the prac-ticality of *** *** has two major subtypes:Esophageal squamous cell carcinoma(ESCC)and esophageal adenocarcinoma(EAC),which have different etiologies and risk *** microbiota can contribute to EC via inflammation-induced carcinogenesis,immunomodulation,lactagenesis,and genotoxin *** infection is said to be inversely related to EAC,protecting against EAC by inducing atrophic gastritis,altering serum ghrelin levels,and triggering cancer cell *** *** infection has no significant association with ESCC,COX-2-1195 polymorphisms and endogenous nitrosamine production can impact the risk of ESCC in ***-infected *** are concerns regarding a plausible increase in EC after *** eradication ***,*** eradication is not associated with an increased risk of EC,making it safe from an EC perspective.

关键词： Helicobacter pylori Helicobacter pylori infection Esophageal cancer Esophageal squamous cell carcinoma Esophageal adenocarcinoma Barrett’s esophagus Microbiota Dysbiosis Eradication

A MATTER OfTRUST: UNPACKING THE ***

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Beijing Review 2024年第1期67卷 18-19页

作者： rick Dunham Tsinghua University in Beijing

As Xi Jinping,then Vice President of China,prepared for high-stakes meetings in the United States,a top Chinese diplomat lamented the"trust deficit"between the nations and said both sides"must give full attention"to"n... 详细信息

关键词： TRUST deepening mutual

Groovy Gadgets:Samsung Galaxy S24 Ultra

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城市漫步（GBA版） 2024年第4期 28-29页

作者： rick Lombardier 不详

On the overall look of the *** include thinner bezels,and a much smaller front-facing camera cutout than the Galaxy S23 Ultra had.

关键词： Galaxy Groovy Ultra

Groovy Gadgets Sony ULT Wear Headphones

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城市漫步（GBA版） 2024年第5期 40-41页

作者： rick Lombardier 不详

for years now,Sony's Extra Bass line of headphones has provided listeners with a powerful tone,and was generally cheaper than the higher ranged 1000X *** the company is looking to pivot their craft into the bass space一without the outdated'extra bass'nametag to go along with *** latest concept from Sony is the ULT Power Sound,something that it is calling the'ultimate step into the evolution'of its portable audio products.

关键词： Sony something portable

Avoiding Tech Neck This painful condition is more than just a pain in the neck

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空中英语教室（高级版．彭蒙惠英语） 2024年第10期 30-31,48页

作者： rick Thiesse 不详

The typical average adult head weighs approximately 10-12 *** did you know that bending it forward at a 45-degree angle to look at a cellphone or tablet can dramatically increase your chances[of having]tech neck?"That's like having an 8-pound bowling ball as your *** you have 72 pounds at your elbow and 96 pounds on your shoulder,"says Brian Langenhorst,industrial and ergonomics specialist at Mayo Clinic Health System in La Crosse,[Wisconsin]."I probably see tech neck on a weekly basis at businesses,schools and industry."

关键词： neck Neck probably